# ANALYSIS OF PROGRESSION OF THE TRANSFORMED PHENOTYPE

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 1993 · $223,266

## Abstract

The objectives of this proposal are to define the cellular, biochemical and
genetic changes associated with progression of the transformed phenotype in
primary and established rat embryo cells transformed by wild-type 5
adenovirus (Ad5) and mutants of Ad5, alone or in combination with
progression promoting genes (oncogenes) and progression suppressing genes
(tumor suppressor genes).  Model cell culture systems will be used which
display discrete and reversible changes in expression of the transformed
state, including morphological transformation, anchorage independence and
oncogenic and metastatic potential.  Progression in Ad5-transformed cells
does not involve alterations in the expression of viral transforming
gene(s), cellular gene(s) involved in expression of the transformed
phenotype in other systems or levels of tumor suppressor gene(s) which
associate with E1A (p300, p107 and p105Rb) or E1B (p53) proteins.  The
process of progression will be investigated using several approaches,
including:  (a) subtractive cloning techniques to identify gene(s)
differentially expressed in transformed cells displaying different states
of progression; (b) the use of caffeic acid phenethyl ester (CAPE) to
select transformed cells displaying a revertant non-transformed
morphological phenotype; (c) the use of human fibroblast DNA expression
vector libraries transcriptionally regulated by an MMTV-inducible promoter,
alone and in combination with CAPE, to select for transformed cells
displaying morphological reversion of the transformed state; and (d) the
use of antisense constructs and suppressor genes to selectively block viral
and cellular gene(s) products which may mediate states of progression in
transformed cells.  By employing the strategies outlined above, new
suppressor gene(s) will be identified which can alter the transformed state
without directly altering the production of oncogene-encoded products.
This relationship between oncogene/anti-oncogene products will be analyzed
directly by employing cloned rat embryo fibroblast (CREF) cells containing
an Ad5 E1A gene under the transcriptional control of an MMTV-promoter.
Once identified and cloned, appropriate gene(s) will be inserted into
expression vectors, reintroduced into cells and evaluated for their effect
on the progression phenotype.  Progression inducer and progression
suppressor gene(s) will also be used to determine expression in other
mammalian progression models.  The present studies will provide important
insights into the process of tumor cell progression and the gene(s) which
mediate and inhibit this process.  This information will prove relevant in
defining the molecular basis of carcinogenesis and in developing strategies
for inhibiting and/or reversing oncogenic transformation and tumor cell
progression.

## Key facts

- **NIH application ID:** 3173271
- **Project number:** 5R01CA035675-10
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **SAM.gov UEI:** F4N1QNPB95M4
- **Principal Investigator:** PAUL B FISHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $223,266
- **Award type:** 5
- **Project period:** 1984-04-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173271

## Citation

> US National Institutes of Health, RePORTER application 3173271, ANALYSIS OF PROGRESSION OF THE TRANSFORMED PHENOTYPE (5R01CA035675-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173271. Licensed CC0.

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